Vitamin D Therapy in Individuals With Prehypertension or Hypertension

Abstract

V itamin D deficiency is a common problem with implications for human health.1 A large body of epidemiological evidence links vitamin D deficiency with a higher risk of cardiovascular disorders, including hypertension. 2,3A meta-analysis of observational studies found that every 16-ng/mL decrease in vitamin D was associated with a 16% higher risk of hypertension. 4 A meta-analysis of population genetic studies suggested that polymorphisms related to Background-A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension. This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited. Methods and Results-A double-blind, randomized, controlled trial was conducted at 4 sites in the United States. We enrolled 534 individuals 18 to 50 years of age with low vitamin D status (25-hydroxyvitamin D levels ≤25 ng/mL) and systolic blood pressure of 120 to 159 mm Hg. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D 3 for 6 months. The primary end point was change in mean 24-hour systolic blood pressure. Secondary end points included change in ambulatory diastolic blood pressure and clinic systolic and diastolic blood pressures. The median age was 38 years, and 62% of participants were men. Forty-six percent of participants were white, and 48% were black. The median 25-hydroxyvitamin D level at baseline was 15.3 ng/mL. Four-hundred fiftyfive participants (85%) had at least 1 follow-up blood pressure measurement; 383 participants (72%) completed the full 6-month study. At the end of the study, there was no significant difference in the primary end point (change in mean 24-hour systolic blood pressure, −0.8 versus −1.6 mm Hg in the high-dose and low-dose arms; P=0.71) or in any of the secondary end points. Furthermore, there was no evidence of association between change in 25-hydroxyvitamin D and change in 24-hour systolic blood pressure at 6 months (Spearman correlation coefficient, −0.05, P=0.34). Results were consistent across prespecified subgroups. Disruption of these receptors in animals is associated with elevated blood pressure, which can be normalized with vitamin D administration. Conclusions-Vitamin 8 Clinical Perspective on p 262These observations raise the possibility that vitamin D supplementation could reduce blood pressure in humans. However, results of randomized, intervention trials have been conflicting, with some studies, but not others, suggesting a benefit. [9][10][11][12][13][14] In most of the trials, blood pressure was not the primary end point, nor was it measured with standardized protocols. These trials also typically randomized <150 participants and included a large proportion of individuals who were already on antihypertensive therapy. Importantly, very few nonwhite individuals have been included in prior studies, despite the high prevalence of both vitamin D deficiency and elevated bloo...

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

“…A recent meta-analysis on a large number of studies found no evidence of vitamin D supplementation on BP reduction (40). Also, two recent RCT in hypertensive patients with low 25(OH)D 3 levels did not find a significant effect of vitamin D supplementation on BP (24,365). Together, these findings do not support the use of vitamin D as treatment for hypertension.…”

Effectiveness of Vitamin D Supplementation for Cardiovascular Health Outcomes

“…Generally, most of the effective trials were of a smaller sample size. Seven RCTs with an apparently appropriate sample size have investigated the effects of VitD on brachial BP, and from these, 6 reported no significant improvement [68,76,77,92,93,94]. Only 1 trial reported significant BP lowering, and this was in a population of black individuals [79]; importantly though, this effect was no longer significant after correcting for between-group differences in BP at baseline.…”

“…The remaining 73% of studies placed no restrictions on baseline serum VitD levels or included a combination of deficient and non-deficient participants (i.e., <30,<40 or <60 ng/ml), which could confound the results. Among the RCTs that included VitD-deficient participants and investigated the effects on brachial BP (n = 8), 6 had no significant effects [64,70,71,77,85,94] and 2 (very short-term; ≤3 months) trials reported an improvement in brachial BP [56,60] (Table 1). None of the RCTs appropriately addressing rule 1 found a significant effect on cfPWV [64,70,71,77,84,85], carotid-radial PWV [75] or brachial-ankle PWV [64].…”

Association between vitamin D levels and arterial hypertension in women at very high cardiovascular risk

“…However there were also trials that showed no effect of vitamin D supplementation on BP. One of them was performed by Arora et al The authors enrolled population of 534 patients aged between 18 and 50 with vitamin D deficiency, but only 28% of them were hypertensive [20]. The strength of this trial was that the patients didn't take antihypertensive drug, but on the other hand, the patients were young and mostly normotensive.…”